title: Cu(II)-disulfide complexes display simultaneous superoxide dismutase- and catalase-like activities.
abstract: Superoxide is a potentially toxic by-product of cellular metabolism. We have addressed here the in vitro ability of complexes formed between copper(II) ions and various biologically-occurring disulfides (RSSR: oxidized glutathione, cystine, homocystine and α-lipoic acid) to react with superoxide. The studied complexes were found to react with superoxide (generated by a xanthine/xanthine oxidase system) at rate constants (kCu(II)-RSSR) close to 10(6)M(-1)s(-1), which are three orders of magnitude lower than that reported for superoxide dismutase (SOD) but comparable to that of several other copper-containing complexes reported as SOD mimetics. The interaction between the tested Cu(II)-RSSR and superoxide, led to the generation and recovery of concentrations of hydrogen peroxide and oxygen that were, respectively, below and above those theoretically-expected from a sole SOD mimetic action. Interestingly, oxygen was generated when the Cu(II)-RSSR complexes were directly incubated with hydrogen peroxide. Taken together, these results reveal that the Cu(II)-RSSR complexes not only have the capacity to dismutate superoxide but also to simultaneously act like catalase mimetic molecules. When added to superoxide-overproducing mitochondria (condition attained by its exposure to diclofenac), three of the tested complexes were able (2-4μM), not only to totally restore, but also to lower below the basal level the mitochondrial production of superoxide. The present study is first in reporting on the potential of Cu(II)-disulfide complexes to act as SOD and catalase like molecules, suggesting a potential for these types of molecules to act as such under physiological and/or oxidative-stress conditions.
authors.affiliation: Facultad de Quimica, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
authors.forename: Margarita E
authors.initials: ME
authors.lastname: Aliaga
authors.forename: Daniela
authors.initials: D
authors.lastname: Andrade-Acuña
authors.forename: Camilo
authors.initials: C
authors.lastname: López-Alarcón
authors.forename: Cristián
authors.initials: C
authors.lastname: Sandoval-Acuña
authors.forename: Hernán
authors.initials: H
authors.lastname: Speisky
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002374:Catalase / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004220:Disulfides; D013481:Superoxides; D003300:Copper; D002374:Catalase; D013482:Superoxide Dismutase
keywords: (Homo)cystine; Catalase mimetic; Copper–disulfide complexes; Oxidized glutathione; Superoxide dismutase mimetic; α-Lipoic acid